Vitiligo is a disorder in which pigment cells within the skin and eyes are destroyed. Melanomas, the biologic opposite of vitiligo, are a malignant proliferation of the same cell line. In horses, pigs and human beings these two disorders commonly occur together within the same host. The frequency of their association suggests that the relationship is not accidental. If the mechanisms which cause vitiligo could be identified, we might be able to use those processes to destroy malignant pigment cells. Our hypothesis to explain the pathogenesis of vitiligo in association with melanomas involves two distinct parts. One concerns the toxicity to pigment cells of the precursors of melanin; the second involves the immune system. We will continue with our experiments to determine the mechanism by which precursors to melanin are toxic for melanocytes. We will use these substances to produce vitiligo in mice and if successful we will continue the studies on mice having melanomas. In the second series of experiments, we shall attempt to produce vitiligo in mice by modifying the immune system. We will use in vitro techniques to confirm the presence of a cellular and/or humoral immune reaction against antigens common to normal and malignant melanocytes. Our studies are applicable to human subjects with primary and/or metastatic melanomas.